Month: September 2018

A major theme that emerges for me over the past few months is on non-medical uses of genetics, made possible by 1) Continued growth of Direct to Consumer (DTC) testing, 2) large scale studies of non-health traits, and 3) increased acceptance of polygenic risk scores, whereby an aggregate score for a given trait is made from small contributions from many genetic markers. This is something we need to talk about.

1) Millions of DTC tests have been sold in the US (over 12 million, according to one estimate from February). A poll found that “Some 17 percent of Americans already have undergone at least one kind of DNA test, and 52 percent of the remainder say they’d like to.”

2) In the last few months, there have been large scale studies of neuroticism, intelligence, social mobility, and on social traits including loneliness. A lot of research into such “social” traits is performed under a health mandate, as many such traits correlate with health outcomes.

3) Polygenic risk scores can be much better at identifying those at risk of serious conditions. That’s the conclusion of a paper and the basis for a new tool that will ingest e.g. 23andMe data and give you a score. From the paper: “The approach identifies 8.0, 6.1, 3.5, 3.2, and 1.5% of the population at greater than threefold increased risk for coronary artery disease, atrial fibrillation, type 2 diabetes, inflammatory bowel disease, and breast cancer, respectively.” These successes, combined with the type of studies I listed above, lead to, for example, educational achievement and cognitive performance polygenic risk scores, explaining 11-13% of variance, 7-10% of variance respectively. Such scores have already make it into DTC tests, for example educational achievement markers are available from Helix.

Needless to say, such scores have the potential for large social implications. The educational achievement study has appeared all over the press, but I have found good critique of possible implications scant. This piece is an exception, one example:

“There’s as much to be learned about the nature of our educational system as about the nature of the individual in this data,” said Mary Helen Immordino-Yang, professor of education, psychology, and neuroscience at the University of Southern California. Specifically, if certain genetic variants are associated with better educational outcomes, then there might be something about the structure of our educational system that’s favoring people with these variants. For example, if the variants were involved in language comprehension, that could tell educators that current teaching methods aren’t working for students who process language differently. That means they should be designing new interventions to accommodate that variation, Belsky said.”

In the light of Ancestry.com and Spotify teaming up to offer playlists based on your results, a critique of how genetic ancestry testing, who focus on the fact your DNA reveals something meaningful about you. This runs from “conflating DNA and cultural identity” (routing for a World Cup team based on results) to “game programs set up to address past injustices” (using results to prove Native American or African ancestry), to reifying race as a meaningful category (citing a study that showed reading about these tests increased beliefs in racial differences).

I think it is worth highlighting what we have learnt about consumer preferences

The Associated Press reports a poll of 1109 adults it performed on questions related to genetic testing (also refed above on number of people interested in genetic testing). On whether people would want to know if DNA showed they had a genetic variant associated with an incurable disease. 60% said Yes, for under 30s the number was 78%. Most (but not all) would tell family members). The poll also asked about the use of DNA by the Feds — “Half of people think genetic data should be used to help solve crimes only with the consent of the person tested, a third think it’s OK without that consent — and 13 percent don’t think law enforcement should use it at all.”

A Pew poll found majority support for gene editing for babies for health reasons. Men and more supportive; religious people are less supportive. If the intervention relies on testing embryos, most are opposed.

A U of Michigan study on patient attitudes to their biobank samples being commercialized. “67 percent of participants agreed that clear notification of potential commercialization of biospecimens is warranted, but only 23 percent were comfortable with such use. Sixty-two percent believed that profits should be used only to support future research, and 41 percent supported sharing profits with the public.”

STAT reports on consumer adoption of genetics in China. Those in the space refer to a particular emphasis on a Chinese fascination of how genetics affects identity and destiny, and, for the generations born under the one child policy, with finding family. Routine newborn genome sequencing is on the cards within the next five years (Veritas already has a product in pilot out there). Because there isn’t an entrenched medical genetics profession, there will be less paternalism about results.

It strikes me that the academic literature is all about efforts to ensure that people’s informed choices are respected. A lot of this type of work, which looks at what those choices are likely to be, happens outside the academic mainstream. This is an observation I intend to check.

A NYTimes Op-Ed that successes of precision medicine and vastly outnumbered by failures. At the ASCO conference, the four precision therapy trials presented with results were all failures, and yet there was no news reporting.

Federal money to develop a system intended to recognize emerging bio threats based on DNA orders placed, to e.g. spot if someone was trying to re-create an extinct virus.

Regulation

An extension to the European Convention on Human Rights and Biomedicine covering genetic tests come into force on July 1, ten years after it was written. It covers “Article 3 – Primacy of the human being: The interests and welfare of the human being concerned by genetic tests covered by this Protocol shall prevail over the sole interest of society or science, ” and bans genetic discrimination. It outlines the procedures involved if a person is not able to give consent, and clarifies that the information from a test should be made available to the person.

A four year effort has culminated in a recommendation not to sequence all newborns, published by the Hastings Center in the context of a whole issue dedicated to investigating the ethics of the issue. Meanwhile, the four year BabySeq project reports a low uptake in the study by parents of newborns — only 10% were interested in an enrollment session, of whom 67% signed up.

Gene therapy trials have traditionally requires an additional layer of oversight, provided by the Recombinant DNA Advisory Committee (RAC). But that special treatment will no longer needed. Gottlieb and NIH Director Francis Collins wrote “there is no longer sufficient evidence to claim that the risks of gene therapy are entirely unique and unpredictable—or that the field still requires special oversight that falls outside our existing framework for ensuring safety.”

In the 1970s, scientists converged on a “14 day rule”: embryos could be studied up to 14 days post fertilization, which is when the “first inklings” of a nervous system first appear, and the point at which the embryo can no longer split. At that time, it wasn’t possible to keep embryos alive in cell culture beyond a few days. Now, scientists are just about at the 14 day limit. To push beyond this limit, some researchers have used “synthetic embryo like structures” made from stem-cells. This piece covers the advances.

Gene drives in mammals reported for the first time — the inheritance of a specific genetic variant went from 50% to 73% in female embryos only, suggesting the controversial tech has a long way to go. (Note that gene drive research in mosquitos is being actively pursued.)

A case of uniparental diploidy, where most of an 11 year old’s cells only have DNA from her father. She has not yet presented malignancy, though all of the other ~20 such cases worldwide have presented malignancy early in life.

An accessible introduction to “Inborn errors of immunity” — where genetics, rather than unspecified bad luck, can lead to someone succumbing to an infection. Knowledge of the underlying genetics can lead to successful therapeutic approaches.

A tool to predict how many SNPs, and hence what sample sizes, are likely to be involved in various traits.

Knowledge of how genetics influences behavior can lead to “free will doubt”, with potential implications for how individuals view justice. In general, free will doubt decreases support for justice based on retribution, towards justice based on consequentialism. A study shows that, while this is true for violent crime, for “low affect” crime, free will doubt actually decreases support for either type of justice.

The genome can gather mutations as we go through life (a phenomena well known as the cause of cancer). A study (and a nice write-up) shows that early life experiences can end up written in your DNA — some genetic mutations in brain cells depend on the amount of maternal care baby mice received.

And finally, a nice piece from science historian Oren Harman on use of the term “gene” — historically and in the future. And another lovely piece about how some of the genes got their names, including the background to “Pray for Elves”, which I learnt originates with someone I used to work with, Prof Mark Yandell.